Effect of Priming in Subpopulations of Peripheral Neutrophils From Patients with Chronic Periodontitis

Fredriksson, M.

doi:10.1902/jop.2012.110584

Cited by 25 publications

(26 citation statements)

References 31 publications

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“…In the present study, cells that showed high-intensity fluorescence (rho+) accounted for 5-7% of unstimulated neutrophils; this proportion corresponds to previous reports (32). Higher baseline ROS production in unstimulated rho+ neutrophils from cord blood, in line with other data, could reflect their higher responsiveness to upregulation of mediators of systemic inflammation, which is also a typical physiological feature of labor (33,34). It could be supposed that circulating rho+ neutrophils represent the first line of defense, but their precise role remains unclear.…”

Section: Discussionsupporting

confidence: 91%

Effects of local anesthetics on the respiratory burst of cord blood neutrophils in vitro

et al. 2016

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Background: Whether local anesthetics exert anti-inflammatory effects in fetal and newborn systemic neutrophils is unclear. The aim of the present study was to assess the effects of bupivacaine and lidocaine on the respiratory burst of cord blood neutrophils in vitro compared with adult cells. Methods: Whole cord blood (n = 12) and control adult blood samples (n = 7) were incubated with bupivacaine (0.0005, 0.005, 0.05, 1 mmol/l) and lidocaine (0.002, 0.02, 0.2, 4 mmol/l) for 1 and 4 h. The production of reactive oxygen species (ROS) by unstimulated neutrophils and the phorbol myristate acetate-induced oxidative burst were assessed by flow cytometry. A subset of neutrophils showing high fluorescence intensity (rho+) was analyzed separately. results: After 1 h incubation, local anesthetics decreased the respiratory burst in whole cord blood and adult neutrophils in a similar manner. At the clinically relevant concentration of 0.0005 mmol/l, bupivacaine was active, but its effect in cord blood cells could not be detected after 4 h. The cord blood rho+ cell subset was unresponsive to the inhibitory action of bupivacaine. In rho+ neutrophils, basal ROS production was stimulated by lidocaine at the lowest concentration tested. conclusion: Bupivacaine and lidocaine can decrease the respiratory burst in neutrophils of term newborns. t he question of the effects of local anesthetics (LAs) on fetal neutrophils arises in the clinical context of the broad application of neuraxial blockade in obstetrics. Epidural technics are the gold standard for labor intrapartum analgesia and are administered to parturients on request. By applying higher doses of LAs through the existing epidural catheter, surgical anesthesia for cesarean delivery may be easily obtained. The fetal and neonatal implications of epidural techniques are mostly considered to be indirect and dependent on modulation of maternal physiology, and are associated with a higher risk of neonatal pyrexia and sepsis evaluation, but not neonatal infection (1-3). The reasons for these findings are not sufficiently clear. However, direct fetal and neonatal effects of LAs as a result of placental drug transfer should not be entirely excluded. LAs administered epidurally enter the maternal systemic circulation and, after crossing the placental barrier, can reach the fetal circulation, with levels approximately one-third to half those seen in the maternal circulation. Furthermore, because of ion trapping and slower elimination, LAs may persist for longer in fetal and neonatal than maternal blood (4). LAs in the fetal systemic circulation have been reported to abolish an offspring's cardiovascular adaptive reaction to asphyxia (5) and have been suggested to affect blood cells. Specifically, bupivacaine has been shown to modify plasma membrane properties of fetal erythrocytes (6). In other studies, lidocaine, a prototypical amino-amide agent administered epidurally for cesarean sections, was suggested to be responsible for the inhibition of natural killer cells and neutrophil a...

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Section: Discussionsupporting

confidence: 91%

Effects of local anesthetics on the respiratory burst of cord blood neutrophils in vitro

et al. 2016

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“…Taking into consideration that one of the most important effects of TNF is the priming of neutrophils to enhance chemotaxis, phagocytosis, and respiratory burst reactions (36)(37)(38), continuous exposure to OMV may prevent TNF-induced influx of neutrophils and neutrophil-mediated clearance of P. gingivalis. However, neutrophil responsiveness to TNF priming in PD patients was equivalent to that in healthy controls (39). Nevertheless, use of peripheral blood neutrophils in the cited study must be critically viewed because only peripheral (i.e., oral) neutrophils are potentially exposed to P. gingivalis OMV.…”

Section: Discussionmentioning

confidence: 98%

Porphyromonas gingivalis Outer Membrane Vesicles Induce Selective Tumor Necrosis Factor Tolerance in a Toll-Like Receptor 4- and mTOR-Dependent Manner

et al. 2016

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f Porphyromonas gingivalis is an important member of the anaerobic oral flora. Its presence fosters growth of periodontal biofilm and development of periodontitis. In this study, we demonstrated that lipophilic outer membrane vesicles (OMV) shed from P. gingivalis promote monocyte unresponsiveness to live P. gingivalis but retain reactivity to stimulation with bacterial DNA isolated from P. gingivalis or AIM2 ligand poly(dA·dT). OMV-mediated tolerance of P. gingivalis is characterized by selective abrogation of tumor necrosis factor (TNF). Neutralization of interleukin-10 (IL-10) during OMV challenge partially restores monocyte responsiveness to P. gingivalis; full reactivity to P. gingivalis can be restored by inhibition of mTOR signaling, which we previously identified as the major signaling pathway promoting Toll-like receptor 2 and Toll-like receptor 4 (TLR2/4)-mediated tolerance in monocytes. However, despite previous reports emphasizing a central role of TLR2 in innate immune recognition of P. gingivalis, our current findings highlight a selective role of TLR4 in the promotion of OMV-mediated TNF tolerance: only blockade of TLR4 -and not of TLR2-restores responsiveness to P. gingivalis. Of further note, OMV-mediated tolerance is preserved in the presence of cytochalasin B and chloroquine, indicating that triggering of surface TLR4 is sufficient for this effect. Taking the results together, we propose that P. gingivalis OMV contribute to local immune evasion of P. gingivalis by hampering the host response. P eriodontitis (PD) is probably the most frequent chronic inflammatory disorder associated with an alteration of the local microbiota. Clinically, release of inflammatory mediators induces collagen degradation and bone resorption, which ultimately result in tooth loss. The carbohydrate-deficient subgingival environment fosters the growth of Porphyromonas gingivalis (1). Tissue degradation caused by enzymes released from bacteria and neutrophils provokes an inflammatory response and supplies bacteria with additional nutrients. This specific milieu permits growth of P. gingivalis, whose sophisticated mechanisms for immune evasion enhance growth of the periodontal biofilm, thus leading to bacterial overgrowth and excessive immune stimulation (2, 3).P. gingivalis releases outer membrane lipophilic microvesicles, which contain lipopolysaccharide (LPS) as a major structural component (4-6). These outer membrane vesicles (OMV) overcome the epithelial barrier, thus transporting LPS and other virulence factors into the host tissue (7). Subsequently, OMV elicit a robust mucosal immune response (8), an effect exploited in OMV-based vaccines (8, 9) and mainly attributed to their LPS content (6). However, unlike LPS from Escherichia coli or Salmonella spp., which are Toll-like receptor 4 (TLR4) agonists, P. gingivalis LPS contains a mixture of chemically diverse lipid A species with distinct immune stimulatory properties (10). Albeit P. gingivalis LPS was formerly thought to act as a TLR2 ligand (11, 12), recent studi...

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“…Most of the current knowledge regarding PMN functionality in the oral cavity is derived from studying oral diseases 11, 12, 13, 14, 15, 16, 17, 18 and little is known about oral health. Only a few small-scale studies have addressed oPMNs in non-diseased individuals.…”

Section: Introductionmentioning

confidence: 99%

Oral polymorphonuclear neutrophil characteristics in relation to oral health: a cross-sectional, observational clinical study

et al. 2016

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Polymorphonuclear neutrophils (PMNs) have a major role in the innate immune system. However, little is known about PMN contribution in relation to oral health. The objective of this study was to investigate the numbers and functional characteristics of oral PMNs (oPMNs) compared with circulatory PMNs (cPMNs). Oral rinse and venous blood samples were obtained from 268 systemically and orally healthy volunteers in a cross-sectional observational study. PMN counts, cell cycle analysis and cellular activation state were investigated. Also, reactive oxygen species (ROS) production was analyzed, with and without bacterial stimulation (Fusobacterium nucleatum). In males, 1.2 × 106±1.0 × 106 oPMNs were collected, and showed a tendency to correlate with the levels of gingival bleeding (r=0.215, P=0.008). Comparable oPMNs counts were found among females (1.0 × 106±0.7 × 106). More late-stage apoptotic/necrotic cells were found among the oPMNs (53.1%) compared with the cPMNs (8.5% P<0.001). Without additional stimulation, oPMNs were more activated than cPMNs, as indicated by higher expression of CD11b, CD63 and CD66b, and higher constitutive ROS levels (P<0.001). Notably, in response to bacterial stimulation, oPMNs released comparable ROS levels as cPMNs (P=0.042). In conclusion, this study provides data on viable oPMNs showing high levels of activation in orally and systemically healthy individuals, free of apparent caries lesions and periodontal disease. These data suggests that although the oPMNs are in a more mature stage of their life cycle compared with the cPMNs, oPMNs are still responsive to stimulation, which indicates their functional potential and possible contribution to a healthy oral ecosystem.

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Effect of Priming in Subpopulations of Peripheral Neutrophils From Patients with Chronic Periodontitis

Abstract: Patients with CP had a subpopulation of peripheral neutrophils that were more responsive to IL-8 priming than controls.

Cited by 25 publications

References 31 publications

Effects of local anesthetics on the respiratory burst of cord blood neutrophils in vitro

Effects of local anesthetics on the respiratory burst of cord blood neutrophils in vitro

Porphyromonas gingivalis Outer Membrane Vesicles Induce Selective Tumor Necrosis Factor Tolerance in a Toll-Like Receptor 4- and mTOR-Dependent Manner

Oral polymorphonuclear neutrophil characteristics in relation to oral health: a cross-sectional, observational clinical study

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